Saphenous vein graft protection: effects of c-myc antisense.
OBJECTIVE
Saphenous vein grafting is associated with extensive medial remodeling, characterized by cellular proliferation, loss of smooth muscle cells, and an inflammatory response. In this study, we examined whether unfavorable responses to vein grafting could be modified by the intraoperative application of c-myc antisense oligomers.


METHODS
The intragraft cell proliferation, macrophage infiltration, and medial preservation were examined in a porcine model in the control and antisense-treated groups (n = 36).


RESULTS
Saphenous veins showed transmural distribution of oligomers within 30 minutes of the ex vivo incubation. A concentration-dependent inhibition of cell proliferation in the media of saphenous grafts was noted 3 days later (0 to 200 mumol/L, p = 0.005). The growth inhibition was sequence-specific, because control oligomers produced only insignificant effects (20 mumol/L). Vascular effects of c-myc antisense were associated with a significant attenuation of macrophage infiltration in saphenous grafts. A concentration-dependent decrease in tissue edema (p = 0.0005) and the attenuated loss of smooth muscle cells (p = 0.002) were noted in the media of the arterialized venous conduits after c-myc antisense.


CONCLUSIONS
Direct application of synthetic DNA to harvested saphenous veins resulted in a rapid transmural distribution. The inhibition of the intragraft cell proliferation in vivo after c-myc antisense was sequence dependent. Decrease in vein graft injury resulted in an attenuated inflammatory response and better medial preservation. These findings provide a rationale for assessment of the long-term effects of vein graft protection with c-myc antisense.
Mannion
J D
JD
Department of Medicine (Cardiology), Thomas Jefferson University, Philadelphia, Pa. 19107, USA.
Ormont
M L
ML
Shi
Y
Y
O'Brien
J E
JE
Chung
W
W
Roqué
F
F
Zalewski
A
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016259:Genes, myc / Q000235:genetics*; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D012501:Saphenous Vein / Q000473:pathology / Q000637:transplantation*; D013552:Swine; D013997:Time Factors; D017539:Tunica Intima / Q000166:cytology; D017540:Tunica Media / Q000166:cytology
D016376:Oligonucleotides, Antisense